This invention relates generally to medical compositions and methods of treatment. More specifically, the present invention relates to compositions and methods for controlling injury response.
Injury response refers to an array of physiological changes. These changes include muscle catabolism, increased energy expenditure, production of cytokines (tumor necrosis factor (TNF) and interleukin-1 (IL-1)) and eicosanoid synthesis. The response may be exaggerated in severe illness or injury.
Limiting the exaggerated injury response may be necessary in order to allow a patient to recover from specific trauma or other injury. There has been some focus on utilizing marine oil alone to influence injury response. Examples include the following publications:
Mascioli et al, "Enhanced Survival to Endotoxin in Guinea Pigs Fed IV Fish Oil Emulsion", Lipids, Vol. 23, No. 6 (1988), pp. 623-625 --considered the hypothesis that fish oils would be protective against endotoxic shock by utilizing an IV preparation of fish oil;
Mascioli et al, "Endotoxin Challenge After Menhaden Oil Diet: Effects on Survival of Guinea Pigs", Am. J. Clin. Nutr. 1989; 49, pp. 277-282 --concludes that feeding animals a diet whose predominant lipid source is fish oil significantly improves survival after endotoxin;
Ogle et al, "An Evaluation of the Effect of Eicosapentaenoic Acid in the Diet on Macrophage PGE Production and Lymphocyte Proliferation in a Burned Guinea Pig Model", Clinical Nutrition (1988) 7; pp. 219-223 --states that results indicate that increasing concentrations of eicosapentaenoic acid (EPA) did not cause significant difference in the total in vitro production of PGE (PGE.sub.2 and/or PGE.sub.3) by LPS-stimulated splenic macrophages except for the diet containing 100% EPA as the lipid component;
Billiar et al, "Fatty Acid Intake and Kupffer Cell Function": Fish Oil Alters Eicosanoid and Monokine Production to Endotoxin Stimulation, Surgery 1988; 104, pp. 343-349 --concludes that further experimental studies and controlled clinical trials are necessary to determine the potential benefit of omega-3 fatty acids in a number of clinical situations;
Swenson et al, "Persistence of Metabolic Effects After Long-Term Oral Feeding of a Structured Triglyceride Derived from Medium-Chain Triglyceride and Fish Oil in Burned and Normal Rats", Metabolism, Vol. 40, No. 5, May 1991, pp. 484-490 --states that a structured triglyceride made from MCT and fish oil induced systemic metabolic changes that persisted far beyond the normal post meal period and thus could only be principally attributed to chronic dietary effects on organ size and membrane composition. The paper concludes that the changes seen in rats earlier fed structured triglycerides were the result of cellular incorporation of omega-3 fatty acids, rather than medium chain fatty acids;
Pomposelli et al, "Attenuation of the Febrile Response in Guinea Pigs by Fish Oil Enriched Diets", Journal of Parenteral and Enteral Nutrition, Vol. 13, No. 2, Mar./Apr. 1989, pp. 136-140 --studied febrile response and in vitro thromboxane B.sub.2 /B.sub.3 production on animals fed diets enriched with fish oil;
Teo et al, "Administration of Structured Lipid Composed of MCT and Fish Oil Reduces Net Protein Catabolism in Enterally Fed Burned Rats" Ann Surg., Vol. 210, No. 1, July 1989, pp. 100-107 --compared the effect of MCT/fish oil versus safflower oil on protein and energy metabolism in enterally fed burned rats;
Hirschberg et al, "The Effects of Chronic Fish Oil Feeding in Rats on Protein Catabolism Induced by Recombinant Mediators", Metabolism, Vol. 39, No. 4, April 10 1990, pp. 397-402 --concludes that feeding fish oil for 6 weeks as opposed to safflower oil benefitted the animals receiving recombinant monokines by reducing whole-body leucine oxidation and by increasing net hepatic protein anabolism presumably at the expense of greater net skeletal protein catabolism; and
Barton et al, "Dietary Omega-3 Fatty Acids Decrease Mortality and Kupffer Cell Prostaglandin E.sub.2 Production in a Rat Model of Chronic Sepsis", The Journal of Trauma, Vol. 31, No. 6, June 1991, pp. 768-774 --tested hypothesis that substitution of omega-3 fats for dietary omega-6 fats would reduce mortality and decrease Kupffer cell prostaglandin E.sub.2 (PGE.sub.2) production in a rat model of chronic sepsis.
See also: Kinney et al, "The Intensive Care Patient", pp. 656-671; and Hellerstein et al, "Interleukin-1-Induced Anorexia in the Rat", J. Clin. Invest., Vol. 84, July 1989, pp. 228-235.
A number of patents and applications have discussed the use of omega-3 fatty acids. These patents and applications include: U.S. Pat. Nos. 5,053,387; 5,034,414; 4,820,731; 4,752,618; 4,678,808; PCT/US/8803037; and PCT/US88/00504. Likewise, a number of publications have considered the use and ratios of fatty acids. See, for example, Broughton et al, "Effect of Increasing the Dietary (N-3) to (N-6) Polyunsaturated Fatty Acid Ratio on Murine Liver and Peritoneal Cell Fatty Acids and Eicosanoid Formation", pp. 155-164, American Institute of Nutrition (1991) and Boudreau et al, "Lack of Dose Response by Dietary N-3 Fatty Acids at a Constant Ratio of N-3 to N-6 Fatty Acids in Suppressing Eicosanoid Biosynthesis from Arachidonic Acid", pp. 111-117, Am. J. Clin. Nutri. 1991; 54.
Despite the research in this area, "[t]here is as yet no consensus as to the ideal percentage of nonprotein calories as fat, the proper time course for initiation of feeding, or the ideal type of fat". Swenson et al, supra at 484.
Excessive marine oil intake can indeed be harmful. Marine oil has been found in some instances to reduce platelet counts and increase bleeding tendencies. Therefore, there has been a reluctance to design certain formulas with marine oils.
Further, commercially available compositions do not provide a composition and/or method that sufficiently limits injury response. Additionally, most marine oil compositions that are available or have been designed do not include essential fatty acids and therefore do not limit injury response. Accordingly, there is a need for a method and composition for limiting the injury response.